Selection of DNA-Encoded Libraries to Protein Targets within and on Living Cells

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Cai B., Kim D., Akhand S., Sun Y., Cassell R. J., ALPSOY A., ...Daha Fazla

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, cilt.141, sa.43, ss.17057-17061, 2019 (SCI-Expanded, Scopus) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 141 Sayı: 43
  • Basım Tarihi: 2019
  • Doi Numarası: 10.1021/jacs.9b08085
  • Dergi Adı: JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.17057-17061
  • Orta Doğu Teknik Üniversitesi Adresli: Hayır

Özet

We report the selection of DNA-encoded small molecule libraries against protein targets within the cytosol and on the surface of live cells. The approach relies on generation of a covalent linkage of the DNA to protein targets by affinity labeling. This cross-linking event enables subsequent copurification by a tag on the recombinant protein. To access targets within cells, a cyclic cell-penetrating peptide is appended to DNA-encoded libraries for delivery across the cell membrane. As this approach assesses binding of DELs to targets in live cells, it provides a strategy for selection of DELs against challenging targets that cannot be expressed and purified as active.